The same protein sequence can be encoded by many different mRNA
sequences because of the degeneracy of the genetic code.
Variations in mRNA sequence can play an important role in regulating
protein expression level; for example, synonymous mutations may alter human
susceptibility to diseases.
We seek to understand the RNA features controlling gene expression.
Analyzing protein expression experiments performed by the Northeast Structural Genomics (NeSG)
Consortium, we find that mRNA folding effects dominate in the head
region (initial 16 codons), while codon usage dominates in the tail
(the remainder). Head and tail have similar overall influence.
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[Supported by a grant from the National Institutes of Health (GM106372)]

Binding and Splicing mRNA

The famous double helical shape of DNA arises when
the bases of the two complementary strands pair.
Base-pairing is also the key to allowing special sites of mRNA
to be recognized and we have developed a tool
BINDIGO to
efficiently calculate free energies to optimally BIND olIGOs (short pieces) of RNA
to long RNA, important for mRNA splicing, siRNA, miRNA, etc.
To predict mRNA splice sites, we have used physical
chemical models (Finding with Binding) and a novel statistical
method (Primary Sequence Ranking).
[Supported by a grant from the National Institutes of Health (GM080690)]

Improving RNA Pseudoknot Models and Algorithms

RNA is more than an intermediary between DNA and proteins, it also
modulates gene expression and catalyzes certain reactions.
Complementary base pairing condenses RNA into complex, compact shapes.
Hairpin or tree-like structures (Fig a) emerge most often, but occasionally the more
complicated pseudoknot fold (Fig b) appears.

Pseudoknots are not common, but have amazing functionality when they do appear,
catalyzing reactions as enzymes or performing other gene regulation functions.
For example, the core of most catalytic RNAs is the interesting pseudoknot fold.
Pseudoknots cannot be predicted using traditional RNA folding algorithms.
Aalberts and his students have been improving models of pseudoknot
structures and have been computing how abundant pseudoknots are.
[Supported by a grant from the National Science Foundation (MCB 0641995)]

Rhodopsin, the optically active molecule in our eyes, changes shape
when it absorbs a photon. This is the fastest photochemical reaction
known --- 200 femtoseconds, less than the time it takes light to cross
the width of your hair. Rhodopsin is a highly efficient system with
very little noise which is one of the reasons we see when our rod cells
are stimulated by only a few photons. I have been developing quantum
mechanical models to study how absorption of light creates compact,
coherent excitations called solitons and how these may induce the
molecular shape change.
[Supported with a Cottrell College Science Award by the Research
Corporation]